2. Academic Validation
  3. Protein phosphatase 1 regulatory subunit 15 A promotes translation initiation and induces G2M phase arrest during cuproptosis in cancers

Protein phosphatase 1 regulatory subunit 15 A promotes translation initiation and induces G2M phase arrest during cuproptosis in cancers

  • Cell Death Dis. 2024 Feb 16;15(2):149. doi: 10.1038/s41419-024-06489-w.
Chunyu Liu # 1,  Liang Chen # 1,  Yukun Cong # 1,  Lulin Cheng 1,  Yujun Shuai 1,  Fang Lv 1,  Kang Chen 1,  Yarong Song 2,  Yifei Xing 3
Affiliations

Affiliations

  • 1 Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China.
  • 2 Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China. tjmusong@126.com.
  • 3 Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China. yfxing@hust.edu.cn.
  • # Contributed equally.
PMID: 38365764 DOI: 10.1038/s41419-024-06489-w
Abstract

Copper ions play a crucial role as cofactors for essential Enzymes in cellular processes. However, when the intracellular concentration of copper ions exceeds the homeostatic threshold, they become toxic to cells. In our study, we demonstrated that elesclomol, as a carrier of copper ions, caused an upregulation of protein Phosphatase 1 regulatory subunit 15 A (PPP1R15A), which plays a role in regulating substrate selectivity of protein Phosphatase 1 during Cuproptosis. Mechanistically, we investigated that PPP1R15A activated translation initiation by dephosphorylating eukaryotic translation initiation factor 2 subunit alpha at the S51 residue through protein Phosphatase 1 and phosphorylating eukaryotic translation initiation factor 4E binding protein 1 at the T70 residue. In addition, PPP1R15A reduced H3K4 methylation by altering the phosphorylation of histone methyltransferases, which led to the silencing of MYC and G2M phase arrest.

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